Whole-body kinetic image of a redox probe in mice using Overhauser-enhanced MRI

• Published in: Free radical biology & medicine Vol. 53; no. 2; pp. 328 - 336
• Main Authors: Kosem, Nuttavut, Naganuma, Tatsuya, Ichikawa, Kazuhiro, Phumala Morales, Noppawan, Yasukawa, Keiji, Hyodo, Fuminori, Yamada, Ken-ichi, Utsumi, Hideo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.07.2012
• Subjects: Animals; Carboxy-PROXYL; clinical trials; Cyclic N-Oxides - pharmacokinetics; Female; free radicals; heart; hydrophobicity; image analysis; Image Processing, Computer-Assisted; kidneys; Kinetics; liver; magnetic resonance imaging; Magnetic Resonance Imaging - instrumentation; Magnetic Resonance Imaging - methods; Mice; Molecular Probes - pharmacokinetics; Nitrogen Oxides - analysis; Nitroxyl radicals; Overhauser-enhanced MRI; Oxidation-Reduction; Phantoms, Imaging; Pharmacokinetic imaging; pharmacokinetics; Pyrrolidines - pharmacokinetics; Redox imaging; Redox probes; Spin Labels; Time Factors; variance; PEDRI; Po/w; EPRI; Redox probes; MRI; EPR; DNP; FOV; ROI; OMRI; TE; Carboxy-PROXYL; NMR; CV; TEPR; Pharmacokinetic imaging; Redox imaging; Overhauser-enhanced MRI; TR; Nitroxyl radicals
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2012.04.026

Overhauser-enhanced MRI (OMRI) enables visualization of free radicals in animals based on dynamic nuclear polarization. Real-time data of tissue redox status gathered from kinetic images of redox-sensitive nitroxyl radical probes using OMRI provided both anatomic and physiological information. Phantom experiments demonstrated the linear correlation between the enhancement factor and the concentration of a membrane-impermeable probe, carboxy-PROXYL (3-carboxy-2,2,5,5-tetramethyl- pyrrolidine-1-oxyl). Whole-body OMRI images illustrated the in vivo kinetics of carboxy-PROXYL for 25min. Initial distribution was observed in lung, heart, liver, and kidney, but not brain, corresponding to its minimal lipophilicity. Based on these images (pixel size, 1.33×1.33mm; slice thickness, 50mm), a time–concentration curve with low coefficient of variance (<0.21) was created to assess pharmacokinetic behaviors. A biexponential curve showed a distribution phase from 1 to 10min and an elimination phase from 15 to 25min. The α rate constant was greater than the β rate constant in ROIs, confirming that its pharmacokinetics obeyed a two-compartment model. As a noninvasive technique, combining OMRI imaging with redox probes to monitor tissue redox status may be useful in acquiring valuable information regarding organ function for preclinical and clinical studies of oxidative diseases. [Display omitted] ► Whole-body redox imaging in a living mouse was performed by OMRI. ► Noninvasive kinetic image of redox probe in many organs was observed simultaneously. ► In vivo concentration of redox probe could be quantified by OMRI. ► Kinetic data by OMRI is useful for real-time redox analysis in animal disease models.